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Record W4413757346 · doi:10.3390/genes16091016

Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

2025· article· en· W4413757346 on OpenAlexaff
Saoud Al‐Khuzaei, Mital Shah, Arun Reginald, Morag Shanks, Penny Clouston, Robert E. MacLaren, Stephanie Halford, Samantha R. De Silva, Susan M. Downes

Bibliographic record

VenueGenes · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRetinal Development and Disorders
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsGenotypePhenotypeMedicineOptometryGeneticsBiologyOphthalmologyGene

Abstract

fetched live from OpenAlex

Purpose: To investigate genotype–phenotype correlations in PRPH2-retinopathies in a cohort of 36 patients from the Oxford Eye Hospital and report on novel pathogenic variants. Methods: Clinical data, including best corrected visual acuities (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) imaging, were analysed. Genetic testing was performed using next-generation sequencing (NGS). Results: In this cohort, 26 different PRPH2 variants, including 8 novel variants, were identified. Variants were clustered in the D2 loop of the protein. A diverse range of phenotypes were observed: pseudo-Stargardt pattern dystrophy (PSPD) (47.2%), adult-onset vitelliform macular dystrophy (AVMD) (22.2%), pattern dystrophy (PD) (25.0%), atypical macular dystrophy (2.8%), and retinitis pigmentosa (RP) (2.8%). The mean age of symptom onset was 44.0 ± 14.4 years. Mean BCVA was 0.20 ± 0.54 logMAR OD and 0.14 ± 0.29 logMAR OS at baseline and 0.33 ± 0.40 logMAR OD and 0.32 ± 0.40 logMAR OS after a mean follow up duration of 6.0 ± 3.2 years (range 1–11 years). A thickened ellipsoid zone (EZ) was noted in 34/36 patients with a mean EZ thickness of 44.3 ± 11.3 µm OD and 42.7 ± 11.6 µm OS. No clear genotype–phenotype correlations were observed. Conclusions: The significant phenotypic range described in this study is consistent with the previously reported phenotypic variability in PRPH2 retinopathy and emphasises the complexity of establishing genotype–phenotype correlations in this disease. The thickness of the EZ on OCT may serve as a useful biomarker in distinguishing PRPH2 retinopathy from other phenocopies. These findings contribute to improved understanding of PRPH2 retinopathy and help inform diagnosis and genetic counselling.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.329

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.233
Teacher spread0.227 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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